The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

Hosseinkhani, Negar; Derakhshani, Afshin; Argentiero, Antonella; Racanelli, Vito; Kazemi, Tohid; Mokhtarzadeh, Ahad; Brunetti, Oronzo; Silvestris, Nicola; Baradaran, Behzad

doi:10.3389/fimmu.2021.676181

Cited by 43 publications

(28 citation statements)

References 86 publications

(144 reference statements)

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“…Although containing a similar molecular sequence with the B7 superfamily, VISTA does not possess ITIM/ITAM (immunoreceptor tyrosine-based activation motif). VISTA is expressed on myeloid cells (e.g., monocytes, conventional DCs, macrophages, and circulating granulocytes), T cells, Tregs, and TILs ( Hosseinkhani et al, 2021 ). There are increasing pieces of evidence showing VISTA as a regulatory immune checkpoint.…”

Section: Biology Of Immune Checkpoint Proteinsmentioning

confidence: 99%

Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases

Cai

Zhan

et al. 2021

Front. Genet.

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The inhibitory regulators, known as immune checkpoints, prevent overreaction of the immune system, avoid normal tissue damage, and maintain immune homeostasis during the antimicrobial or antiviral immune response. Unfortunately, cancer cells can mimic the ligands of immune checkpoints to evade immune surveillance. Application of immune checkpoint blockade can help dampen the ligands expressed on cancer cells, reverse the exhaustion status of effector T cells, and reinvigorate the antitumor function. Here, we briefly introduce the structure, expression, signaling pathway, and targeted drugs of several inhibitory immune checkpoints (PD-1/PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, and IDO1). And we summarize the application of immune checkpoint inhibitors in tumors, such as single agent and combination therapy and adverse reactions. At the same time, we further discussed the correlation between immune checkpoints and microorganisms and the role of immune checkpoints in microbial-infection diseases. This review focused on the current knowledge about the role of the immune checkpoints will help in applying immune checkpoints for clinical therapy of cancer and other diseases.

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Section: Biology Of Immune Checkpoint Proteinsmentioning

confidence: 99%

Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases

Cai

Zhan

et al. 2021

Front. Genet.

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“…Multiple cell types can express VSIR, such as cancer cells, neutrophils, monocytes, macrophages, dendritic cells (D.C.s), and T cells in humans and mice ( Flies et al, 2011 ; Lines et al, 2014 ). Previous studies have found that VSIR is widely involved in various physiological and pathological processes, including regulating peripheral tolerance, inducing T cell activation and differentiation, and mediating tumor immunity ( ElTanbouly et al, 2019 ; Hosseinkhani et al, 2021 ). Thus, growing evidence indicated that VSIR might be a promising target for tumor immunotherapeutic intervention in the TME.…”

Section: Introductionmentioning

confidence: 99%

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Liu

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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VSIR is a critical immunomodulatory receptor that inhibits T cell effector function and maintains peripheral tolerance. However, the mechanism by which VSIR participates in tumor immunity in the pan-cancer tumor microenvironment remains unclear. This study systematically explored the prognostic and immune profile of VSIR in the tumor microenvironment of 33 cancers. We compared the expression patterns and molecular features of VSIR in the normal and cancer samples both from the public databases and tumor chips. VSIR level was significantly related to patients’ prognosis and could be a promising predictor in many tumor types, such as GBM, KIRC, SKCM, READ, and PRAD. Elevated VSIR was closely correlated with infiltrated inflammatory cells, neoantigens expression, MSI, TMB, and classical immune checkpoints in the tumor microenvironment. Enrichment signaling pathways analysis indicated VSIR was involved in several immune-related pathways such as activation, proliferation, and migration of fibroblast, T cell, mast cell, macrophages, and foam cell. In addition, VSIR was found to widely express on cancer cells, fibroblasts, macrophages, and T cells in many tumor types based on the single-cell sequencing analysis and co-express with M2 macrophage markers CD68, CD163 based on the immunofluorescence staining. Finally, we predicted the sensitive drugs targeting VSIR and the immunotherapeutic value of VSIR. In sum, VSIR levels strongly correlated with the clinical outcome and tumor immunity in multiple cancer types. Therefore, therapeutic strategies targeting VSIR in the tumor microenvironment may be valuable tools for cancer immunotherapy.

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“…Therefore, mAbs targeting immune checkpoints enhance T cells' antitumor immune response and improve antitumor defense [7,13]. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1), as well as the B7 family of immune checkpoints, could be considered to be the main immunotherapy targets to inhibit tumor growth in a variety of cancers [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Colorectal Cancer: Challenges and Future Prospects

et al. 2021

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Immunotherapy is a new pillar of cancer therapy that provides novel opportunities to treat solid tumors. In this context, the development of new drugs targeting immune checkpoints is considered a promising approach in colorectal cancer (CRC) treatment because it can be induce specific and durable anti-cancer effects. Despite many advances in the immunotherapy of CRC, there are still limitations and obstacles to successful treatment. The immunosuppressive function of the tumor microenvironment (TME) is one of the causes of poor response to treatment in CRC patients. For this reason, checkpoint-blocking antibodies have shown promising outcomes in CRC patients by blocking inhibitory immune checkpoints and enhancing immune responses against tumors. This review summarizes recent advances in immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3 in CRC, and it discusses various therapeutic strategies with ICIs, including the double blockade of ICIs, combination therapy of ICIs with other immunotherapies, and conventional treatments. This review also delineates a new hopeful path in the combination of anti-PD-1/anti-PD-L1 with other ICIs such as anti-CTLA-4, anti-LAG-3, and anti-TIM-3 for CRC treatment.

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The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

Cited by 43 publications

References 86 publications

Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases

Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases

Identify the Prognostic and Immune Profile of VSIR in the Tumor Microenvironment: A Pan-Cancer Analysis

Immune Checkpoint Inhibitors in Colorectal Cancer: Challenges and Future Prospects

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